PB1949: ELTROMBOPAG IN CHINESE PATIENTS WITH REFRACTORY OR RELAPSED SEVERE APLASTIC ANEMIA: A NON-RANDOMIZED, OPEN-LABEL, MULTICENTER, PHASE II STUDY ASSESSING THE SAFETY AND EFFICACY OF ELTROMBOPAG
Authors: H. Chang, G. He, R. Fu, F. Li, B. Han, T. Li, L. Liu, H. Mittal, H. Jin, F. Zhang
Journal: HemaSphere (2022)

Background: Severe aplastic anemia (SAA) is a life-threating bone marrow failure disorder characterized by pancytopenia and hypocellular bone marrow. SAA that does not respond to or relapses after first-line immunosuppressive therapy (IST) is known as refractory or relapsed (R/R) SAA. For Chinese patients with R/R SAA, there is no established standard of care other than transfusion support and treatment of infections. Evidence suggests that, even with support, a substantial proportion of patients with R/R SAA die within 5 years of diagnosis. There is evidence that eltrombopag can improve response rates in patients with R/R SAA. Eltrombopag is approved in the United States and Europe for the treatment of SAA following an insufficient response to IST. Eltrombopag is not currently approved for the treatment of SAA in China. Aims: To assess eltrombopag efficacy and safety in Chinese patients with R/R SAA. Methods: This Phase II, non-randomized, multicenter, open-label study (NCT03988608) enrolled Chinese adult patients (≥18 yrs) with R/R SAA. The starting dose of eltrombopag was 25 mg/day, which increased by 25 mg/day every 2 wks based on the total platelet count, up to a maximum dose of 150 mg/day. The primary endpoint was hematologic response (HR) rate at Wk 26, defined as the proportion of patients meeting any of the International Working Group criteria for changes in platelet, hemoglobin, or neutrophil count. Secondary endpoints included HR rate at Wk 13 (and 1 yr; data not shown); time to HR and its duration; changes in transfusion need; safety outcomes; and the rate of clonal evolution. Results: A total of 20 patients were enrolled. The median (range) age was 37.5 (18-69) yrs, 75% were male, and all (100%) patients were Asian. The median (range) duration of exposure to eltrombopag was 258.5 (69-443) days, and the median (range) daily dose was 122.8 (26-138) mg/day. The primary endpoint (HR at Wk 26) was met in 70% (14/20) of patients (7/14 bi-lineage; 2/14 tri-lineage) (Fig. 1). The secondary endpoint (HR at Wk 13) was met in 65% (13/20) of patients (4/13 bi-lineage; 1/13 tri-lineage) (Fig. 1). The median (90% confidence interval) time to HR was 10 (8-12) wks. Of the 14 patients who were red blood cell (RBC) transfusion-dependent at baseline, 10 (71%) and 8 (57%) had reduced RBC transfusion or were transfusion-independent vs baseline at Wks 13 and 26, respectively. Of the 10 platelet transfusion-dependent patients at baseline, 7 (70%) and 8 (80%) had reduced platelet transfusion or were transfusion-independent at Wk 13 and 26, respectively. Adverse events (AEs) occurred in 19/20 patients (95%), with 70% (14/20) of patients experiencing a treatment-related AE (TRAE) and 15% (3/20) of patients having a grade ≥3 TRAE. The most common all-grade AE was upper respiratory tract infection (30%). There were 2 cases of treatment-related severe AEs (osteonecrosis [n=1]; groin pain [n=1]). One death from gastrointestinal bleeding (not considered study drug-related) was reported 45 days after last eltrombopag dose. One case of transient clonal evolution (abnormal karyotype present at Wk 13; absent at Wk 26) was reported. Image:Summary/Conclusion: Overall, 70% of patients met the primary endpoint of HR at Wk 26, with more than half of patients reporting reduced transfusion need during the study. Safety findings were consistent with the established safety profile of eltrombopag. Although the sample size was small, this is the first prospective study to show that eltrombopag is efficacious and has a favorable safety profile in a Chinese population with R/R SAA.